Caffeine is an inhibitor of DNA repair in Chinese hamster V79 cells, but has no significant effect (at concentrations up to 1 mM added from 1 to 24 hrs after mutagen) on the N-acetoxy-2-acetyl aminofluorene (AcAAF)-induced frequency of thioguanine (TG)-resistant cells. In contrast, the AcAAF-induced transformation of normal Syrian hamster embryo cells to a neoplastic state can be enhanced 15-fold by post treatment with caffeine. Since the two cell types were shown to differ both qualitatively and quantitatively in their mechanisms of DNA repair, it is not possible to relate mutagenesis to malignant transformation until both assays are performed with normal Syrian hamster cell cultures. Methods for selecting TG-resistant V79 cells were found to be inadequate for the selection of TG-resistant mutants in Syrian hamster embryo cell cultures. New procedures were devised that have permitted the detection of TG-resistant colonies that may also be mutants. Application of these new selection procedures to a transformed line of Syrian hamster cells has shown that AcAAF induces the same mutant frequency as in V79 cells.